Control Of Glomerular Filtration Rate Research Articles

Specifičnost antibiotske terapije kod pacijenata sa hroničnom insuficijencijom bubrega

Chronic kidney diseases cause disruption of kidney function, but also of other organs which affects both the pharmacodynamics and the pharmacokinetics of many drugs. Prescribing drugs to patients with chronic kidney disease requires knowledge of changes in absorption, distribution, metabolism and excretion of drugs and their metabolites. Avoiding nephrotoxic drugs is the most important principle that we must follow in patients with chronic kidney disease. If administration of nephrotoxic drugs is necessary, regular control of glomerular filtration rate, serum electrolyte concentration, and serum drug concentration is required if possible. The dosing of drugs in patients with chronic renal insufficiency is very delicate, both when determining the initial dose and during the maintenance dose, so it is necessary to adjust the doses for each patient individually, depending on the degree of kidney damage. For most drugs, there are recommendations from the Agency for Drugs and Medical Devices of the Republic of Serbia on how to correct the dose of the drug in chronic kidney failure. If such a recommendation does not exist, general rules are used: the maintenance dose can be adapted to kidney function by reducing the dose, extending the intervals in which the unchanged dose of the drug is administered, or a combination of these two methods. In patients with chronic kidney damage, the infection accelerates the progression towards the terminal stage, when it is necessary to apply one of the methods to replace kidney function. The infection should be treated with appropriate doses of antibiotics and/or antifungals and for a sufficient period of time. Likewise, in dialysis patients, there are various causes of infections that must also be adequately treated in order not to compromise the dialysis method or endanger the patient's life. There are recommendations for the use of antibiotics and antimycotics in these cases, which should be applied and adjusted to the individual patient. In intensive care units, in hemodynamically unstable patients with sepsis and acute chronic kidney failure, instead of intermittent hemodialysis, the following methods can be used: prolonged intermittent hemodialysis (PID) and continuous procedures - continuous venovenous hemodialysis (CVVHD), continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF). The dosage of antibiotics in these patients is specific and adjusted to the individual patient and his kidney function. Peritoneal dialysis patients in the terminal phase of chronic kidney failure are at risk of developing peritonitis. The guides describe which antibiotics are used to start the treatment of peritonitis and how the antibiotics are then adjusted, according to the causative agent, after the dialysate culture is obtained. Treatment of peritonitis is mainly by intraperitoneal administration of antibiotics, but it is also possible with oral or parenteral antibiotics, i.e. their combination. The guidelines describe the initial and maintenance doses of antibiotics and antifungals. If treatment is not started on time, the dialysis method may be compromised and the patient may die. If fungi are isolated by culture, the treatment of the patient with peritoneal dialysis is stopped and the dialysis catheter is removed, and the treatment is continued with the administration of antibiotics intravenously.

New Mechanism for the Sex Differences in Salt-Sensitive Hypertension: The Role of Macula Densa NOS1β-Mediated Tubuloglomerular Feedback.

Females are relatively resistant to salt-sensitive hypertension than males, but the mechanisms are not completely elucidated. We recently demonstrated a decisive role of macula densa neuronal NOS1β (nitric oxide synthase β)-mediated tubuloglomerular feedback (TGF) in the long-term control of glomerular filtration rate, sodium excretion, and blood pressure. In the present study, we hypothesized that the macula densa NOS1β-mediated TGF mechanism is different between male and female, thereby contributing to the sexual dimorphism of salt-sensitive hypertension. We used microperfusion, micropuncture, clearance of fluorescein isothiocyanate-inulin, and radio telemetry to examine the sex differences in the changes of macula densa NOS1β expression and activity, TGF response, natriuresis, and blood pressure after salt loading in wild-type and macula densa-specific NOS1 knockout mice. In wild-type mice, a high-salt diet induced greater increases in macula densa NOS1β expression and phosphorylation at Ser 1417, greater nitric oxide generation by the macula densa, and more inhibition in TGF response in vitro and in vivo in females than in males. Additionally, the increases of glomerular filtration rate, urine flow rate, and sodium excretion in response to an acute volume expansion were significantly greater in females than in males. The blood pressure responses to angiotensin II plus a high-salt diet were significantly less in females than in males. In contrast, these sex differences in TGF, natriuretic response, and blood pressure were largely diminished in knockout mice. In conclusion, macula densa NOS1β-mediated TGF is a novel and important mechanism for the sex differences in salt-sensitive hypertension.

Abstract 144: Macula Densa NOS1β-Mediated TGF Response Plays an Important Role in the Sex Differences in Salt-Sensitive Hypertension

Females are resistant to salt-sensitive hypertension than males, but the mechanisms are not completely elucidated. We recently demonstrated that a decisive role of macula densa neuronal nitric oxide synthase β (NOS1β) in the tubuloglomerular feedback (TGF) response, long-term control of glomerular filtration rate (GFR), sodium excretion and blood pressure. Thus, in this study, we tested a hypothesis that high salt diet-induced upregulation of NOS1β in the macula densa is exaggerated in females than males, which induces more inhibition in TGF response, thereby facilitating sodium excretion and contributing to the resistance to salt-sensitive hypertension. We used microperfusion, micropuncture, clearance of FITC–insulin and radio telemetry to examine the sex differences in macula densa NOS1β expression, nitric oxide (NO) generation, TGF response, kidney clearance function and mean arterial pressure (MAP) in response to a high salt diet in C57BL/6 and macula densa–specific NOS1 knockout (KO) mice. In C57BL/6 mice, males and females had comparable basal levels in macula densa NOS1β expression, NO generation, TGF response and MAP. An 2-week high salt diet resulted in more increases of NOS1β expression in female mice than male mice (3.4±0.3-fold vs. 1.7±0.1-fold), greater increases of NO generation by the macula densa in female mice than male mice (99.1±19.8 % vs. 55.6±11.6 %), and more attenuation in TGF responses in vivo (48.7±7.2 % vs. 25.5±2.9 %) as well as TGF response in vitro (58.5±5.6 % vs. 33.7±9.3 % )in female mice than male mice. Additionally, in response to a 2-week high salt diet along with low dose Ang II, the MAP increased by 13.7±4.2 mmHg in females and 35.4±5.6 mmHg in males with a sex difference of 21.7±4.7 mmHg. In the KO mice, the high salt diet had no significant effects on the macula densa NOS1β expression, NO generation, TGF response in vivo or in vitro in both females and males. Moreover, in response to the high salt diet along with low dose Ang II, the MAP increased by 41.7±4.1 mmHg in KO females and 52.6±3.8 mmHg in KO males with a sex difference of 10.9±3.1 mmHg, which was significantly reduced compared with C57BL/6 mice. In conclusion, macula densa NOS1β-mediated TGF response plays an important role in the sex difference in salt-sensitive hypertension.

Sympathetic innervation of the kidney in health and disease: Emphasis on the role of purinergic cotransmission

There is introductory information about non-synaptic transmission at sympathetic neuroeffector junctions and sympathetic nerve cotransmission utilizing noradrenaline and ATP as cotransmitters. Then the organzation and location of sympathetic nerves in different sites in the kidney are described, including renal arteries, juxtaglomerular arterioles and renal tubules. Sympathetic nervous control of glomerular filtration rate and of renin secretion are discussed. Evidence, obtained largely from experiments on animals, for sympathetic nerve modulation of the transport of water, sodium and other ions in the collecting duct of the nephron is described. Finally, there is coverage of the roles of sympathetic nerves in renal diseases, including hypertension, diabetes, hypothyroidism and ischaemia.

Tubuloglomerular feedback control of glomerular filtration rate is preserved in connexin 40‐deficient mice

The gap junctional protein connexin 40 (Cx40) is highly expressed in the extraglomerular mesangium connecting the tubular epithelium at the macula densa and the afferent arteriole. Participation of Cx40 in juxtaglomerular communication is suggested by the finding that the expression of renin and the localization of renin‐expressing cells are greatly abnormal in Cx40‐deficient mice. In the present experiments we have therefore used wild type and Cx40−/− mice to determine the role of connexin 40 in tubuloglomerular feedback (TGF). Stop flow pressure (Psf) assessed by micropuncture fell from 40.0±1.7 to 34.5±1.7 mmHg in C57Bl/6 wild type mice, and from 31.3±1.0 to 26.9±0.9 mmHg in Cx40−/− mice. Psf changes of 5.5±0.5 mmHg in wild type and of 4.4±0.5 in Cx40−/− mice were not significantly different (p=0.125). Psf values were significantly lower in Cx40−/− than wild type mice at all flow rates. Arterial blood pressure was not different between wild type and Cx40−/− mice. Glomerular filtration rate (GFR) of conscious mice was lower in Cx40−/− than wild types and this difference increased with aging. We conclude that TGF responsiveness is well maintained in the absence of connexin 40 suggesting that coupling through this dominant mesangial protein is not required for tubulo‐vascular communication. Renal vascular resistance appears to be elevated in Cx40−/− mice, perhaps a consequence of the elevated plasma renin levels.

Making sense of the sensor: Mysteries of the macula densa

Increases in luminal NaCl concentration at the macula densa (MD), the sensing element, activate tubuloglomerular feedback (TGF). MD cell volume increases when increments are isosmotic and shrinks if osmolality increases. This interesting finding introduces additional complexity to the role of the MD in TGF.

Co-expression of type 1 angiotensin II receptor (AT1R) and renin mRNAs in juxtaglomerular cells of the rat kidney

Physiological and ligand binding studies have shown that Angiotensin II (AII) exerts various functions along different segments of the nephron, via the type-1 receptor (AT1R), resulting in the control of glomerular filtration rate (GFR) and water and salt homeostasis. We have used the recently cloned AT1R cDNA to localize, by in situ hybridization, the cells expressing AT1R mRNA in the rat kidney. On serial sections, juxtaglomerular (JG) renin secreting cells, identified by hybridization with a renin cRNA probe, also co-express AT1R mRNA. The co-expression of AT1R and renin mRNAs in the same cells documents visually the direct feedback control of AII on renin secretion. AT1R mRNA was also present in known target cells for AII: proximal convoluted tubule, mesangium and vasa recta.

Co-expression of type 1 angiotensin II receptor (AT1R) and renin mRNAs in juxtaglomerular cells of the rat kidney.

Physiological and ligand binding studies have shown that Angiotensin II (AII) exerts various functions along different segments of the nephron, via the type-1 receptor (AT1R), resulting in the control of glomerular filtration rate (GFR) and water and salt homeostasis. We have used the recently cloned AT1R cDNA to localize, by in situ hybridization, the cells expressing AT1R mRNA in the rat kidney. On serial sections, juxtaglomerular (JG) renin secreting cells, identified by hybridization with a renin cRNA probe, also co-express AT1R mRNA. The co-expression of AT1R and renin mRNAs in the same cells documents visually the direct feedback control of AII on renin secretion. AT1R mRNA was also present in known target cells for AII: proximal convoluted tubule, mesangium and vasa recta.

L-arginine/nitric oxide pathway: a possible signal transduction mechanism for the regulation of the chemokine IL-8 in human mesangial cells.

The central function of the mesangial cell within the kidney is the control of glomerular filtration rate primarily via the regulation of mesangial cell tone. A secondary function of this specialised pericyte is to maintain the integrity of the glomerulus via matrix synthesis and provide support for the capillary loops. The elicitation of neutrophils and monocytes from the circulation into the inflamed glomerulus accompanied by proliferation of resident mesangial cells and expansion of mesangial matrix are prominent features of immunologically mediated glomerulonephritis (1).

Natriuretic and Vasoactive Hormones and Glomerular Hyperfiltration in Hyperglycaemic Type 2 Diabetic Patients: Effect of Insulin Treatment

Evidence that an increase in plasma atrial natriuretic peptide (ANP) concentrations mediates, at least in part, glomerular hyperfiltration in diabetic rats prompted us to study the relationship between ANP and renal haemodynamics in hyperfiltering type 2 diabetic patients in association with other hormones implicated in the control of glomerular filtration rate (GFR) (catecholamines, vasopressin, renin) and in sodium tubular transport (aldosterone, ouabain-displacing factor, ODF). Since hyperglycaemia is also associated to hyperfiltration, diabetic patients who presented with secondary drug failure were studied both in hyperglycaemic and in normoglycaemic condition. For this purpose, 11 normotensive non-macroproteinuric hyperfiltering patients with type 2 diabetes were treated with an 8-day continuous insulin infusion (days 0-7). Dehydration was prevented or corrected and natriuresis was on day 0 above 100 mmol/day. The following parameters were determined on days 0 and 7: GFR and renal plasma flow (RPF) by 99mTc-DTPA and 131I-hippuran clearances; the extracellular volume, assimilated to the DTPA diffusion volume; urinary ODF by receptor-binding assay and urinary as well as plasma catecholamines by HPLC after extraction on alumin. Plasma ANP and antidiuretic hormone (ADH) were measured by radioimmunoassay after extraction on phenyl-silylsilica (ANP) and with ether (ADH). Unextracted plasma was used for radioimmunological measurement of plasma renin activity and aldosterone. When correcting hyperglycaemia to normoglycaemia GFR decreased from high to normal mean value (138 +/- 27 and 115 +/- 6 ml/min, p < 0.001), RPF followed the same trend, and the DTPA diffusion volume did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucocorticoids and control of glomerular filtration rate.

Glucocorticoids given acutely or chronically at physiological/pharmacological doses increase GFR in both experimental animals and humans. Glomerular micropuncture studies have shown that in the normal rat kidney, glucocorticoids vasodilate both the preglomerular and efferent resistances and result in an increase in glomerular plasma flow, which is the sole factor responsible for the increase in GFR. However, the mechanism(s) initiating these alterations in the glomerular microcirculation remain obscure. The glucocorticoid-induced increase in GFR does not appear to be due to volume expansion or alteration in tubulo-glomerular feedback activity. Chronic glucocorticoid administration has been shown to increase renal prostaglandin synthesis in some but not all species; however, a link between increased prostaglandin production and glucocorticoid-induced increase in GFR has not been established. A number of studies have examined glucocorticoid-induced alterations in renal vascular reactivity to vasoconstrictor agonists and the data have been conflicting. The suggestion that glucocorticoid-stimulated ANP production evokes the increase in GFR is unlikely to be correct based on substantial differences in the glomerular hemodynamic changes seen with ANP or glucocorticoids. An interesting proposal that appears well worth exploring is that glucocorticoids may increase GFR through their effects on catabolism of proteins to increase production of amino acids. Amino acid infusion markedly elevates GFR and has a similar glomerular hemodynamic profile as that of glucocorticoids. By virtue of their action to increase GFR, glucocorticoids increase the rate of electrolyte and water delivery into the nephron. Therefore, glucocorticoid-induced alterations in electrolyte and water excretion may be secondary to an elevation in GFR, in addition to direct actions of glucocorticoids on the tubule. Also, by determining the hemodynamic state of the kidney, and hence, rate of fluid delivery through the nephron, glucocorticoids may influence the sensitivity of the nephron to regulatory influences. Glucocorticoids have their most profound effect (especially clinically) by modifying the immunological or cellular mechanisms responsible for glomerular injury. Less important is their ability to increase GFR. In view of some evidence that suggests increasing glomerular pressure accelerates the progression of established renal disease, some might speculate that glucocorticoids actually increase glomerular damage under certain conditions.

Chlorothiazide effect on feedback-mediated control of glomerular filtration rate.

We examined the effect of chlorothiazide (CTZ) on the tubuloglomerular (TG) feedback system in anesthetized Sprague-Dawley rats. During infusion of CTZ (0.25 mg.kg body wt-1.min-1) we found that whole kidney glomerular filtration rate (GFR) decreased by 19% (1.0 +/- 0.1 vs. 0.8 +/- 0.1 ml/min; P less than 0.005). To asses the activity of the TG feedback system during CTZ administration we compared measurements of single-nephron (SN)GFR from tubule fluid sampled separately at proximal and distal sites. During CTZ administration, distally measured SNGFR decreased significantly by 16% (27.3 +/- 1.3 vs. 22.9 +/- 1.1 nl/min; P less than 0.025), whereas proximally measured SNGFR was unchanged. Thus the difference in SNGFR between proximal and distal determination increased during CTZ infusion (4.7 +/- 0.7 vs. 7.7 +/- 0.7 nl/min; P less than 0.025), indicating that CTZ suppresses GFR by TG feedback. Na, K, and Cl concentrations measured in the late proximal tubule fluid during control and CTZ infusions were similar. In early distal tubule fluid samples K and Cl concentrations were unaffected by CTZ infusion, whereas Na concentrations increased by 32% (47.9 +/- 2.7 vs. 63.1 +/- 2.4 mM; P less than 0.001). Proximal tubule microperfusion with 1.0 mM CTZ decreased transport rates of Na and water by approximately 40%, whereas the transport rate of Cl was not affected. In conclusion our results indicate that CTZ reduces GFR by activating TG feedback. The mechanism by which this occurs is in part due to an increase in the strength of the signal.

Role of glomerular prostanoid in control of glomerular filtration rate in rats.

It is generally accepted that the main action of glomerular prostanoids (GPs) on glomerular filtration rate (GFR) is to modulate the activity of different vasoconstrictors, specially in states of renal hypoperfusion. However it was also suggested that GPs may directly affect GFR. The present study was focused on this last hypothesis, in different experimental models, in rats. In adriamycin induced acute renal failure, the transient decrease of GFR is associated with higher levels of thromboxane B2. Later on, when GFR returns to normal, vasodilator prostaglandins synthesis was also increased. In captopril induced renal failure in Na depleted rats (where GPs synthesis remained normal), stimulation of PGE2 and PGI2 production by K and NaCl was associated with a significant improvement of GFR. Furthermore, the increase in GFR induced by NaCl was prevented by inhibition of prostaglandin synthesis. Infusion of atrial natriuretic peptide in euvolemic rats induce a marked elevation both of GFR and PGE2 synthesis. It was abolished by previous administration of prostaglandin synthesis inhibitor. In conclusion, glomerular prostanoids may influence GFR, either directly, or as mediator or modulator of other vasoactive hormones.

The control of glomerular filtration rate and renal blood flow in chronically volume-expanded rats.

1. Chronic volume expansion by dietary salt loading practically abolishes tubuloglomerular feed-back (TGF) by means of a humoral inhibitor in tubular fluid. Elimination of the vasoconstrictor influence of feed-back does not, however, increase glomerular filtration rate (GFR) and renal blood flow (RBF), implying that chronic salt loading induces additional preglomerular vasoconstriction. This being so, the feed-back response which, although absent in free-flowing nephrons, can still be elicited by loop of Henle perfusion with Ringer solution, should be essentially normal, except that nephron GFR at any loop perfusion rate should be lower than in controls. Persistence of RBF, GFR and nephron GFR autoregulation would imply that autoregulation is achieved by a preglomerular resistance control system independent of feed-back. 2. These hypotheses were tested by clearance and micropuncture experiments in rats chronically fed a diet containing 40 g NaCl (kg food)-1. 3. RBF and GFR autoregulation indeed persisted, the former down to 90 mmHg compared with 105 mmHg in controls. In controls, nephron GFR measured distally was autoregulated down to 90 mmHg whereas that measured proximally was autoregulated only above 105 mmHg. In high-salt rats nephron GFR from both sites was autoregulated to 90 mmHg. 4. Loop of Henle perfusion with homologous tubular fluid in high-salt rats confirmed attenuation of feed-back. Loop perfusion with Ringer solution yielded a response comparable to that in controls (maximal reduction of nephron GFR to 57%, compared with 56% in controls). Absolute nephron GFR at any loop perfusion rate was lower in high-salt rats than in controls. 5. These observations confirm the initial hypotheses. Considering feed-back and autoregulation as independent, preglomerular resistance control mechanisms, together with elementary haemodynamic considerations, allows formulation of a renal haemodynamics model whose quantitative predictions regarding characteristics of RBF, GFR and feed-back control are remarkably consistent with the literature.

Response of atrial natriuretic peptide in plasma and urine to changes in dietary intake of sodium chloride in man.

Plasma concentration and urinary excretion of immunoreactive human atrial natriuretic peptide (ir-hANP), aldosterone, and vasopressin were measured, and renal function and blood pressure were determined in six healthy male subjects in three periods of different sodium intake: the control (172 mEq/day), low (20 mEq/day), and high (285 mEq/day) sodium period. Both plasma concentration and urinary excretion of ir-hANP increased significantly in the high sodium period but did not change between the control and low sodium periods. On the contrary, aldosterone increased and vasopressin decreased in the low sodium period but did not change between the control and high sodium periods. These results may point out the reciprocal action of both endocrine systems. The glomerular filtration rate changed in parallel with sodium intake whereas the fractional excretion of sodium decreased only in the low sodium period, probably reflecting the action of aldosterone. It is concluded from these results that the atrial peptide may be an important component in the regulation of body fluid in the high sodium loading of physiological range but its action may be limited to the control of glomerular filtration rate.

The renal action of atrial natriuretic peptide during control of glomerular filtration

Studies were performed in anesthetized dogs (N = 7) to determine the effects of synthetic atrial natriuretic peptide (ANP) on sodium excretion in the presence and absence of control of glomerular filtration rate produced by suprarenal aortic clamping. Intrarenal infusion of synthetic atrial natriuretic peptide (0.3 micrograms/kg/min) significantly increased glomerular filtration rate from 29.3 +/- 3.0 to 43.2 +/- 4.4 ml/min, urinary sodium excretion from 20.1 +/- 10.3 to 223.3 +/- 52.3 microEq/min, fractional sodium excretion from 0.47 +/- 0.19 to 3.75 +/- 0.59%. In contrast, aortic clamping blocked the increase in glomerular filtration rate in association with an attenuated natriuresis. Urinary sodium excretion increased from 6.3 +/- 2.3 to 68.3 +/- 23.4 microEq/min and fractional sodium excretion increased from 0.15 +/- 0.04 to 0.90 +/- 0.30%. Despite this differential response in glomerular filtration rate and sodium excretion, whole kidney fractional delivery of sodium from the proximal tubule as estimated by the fractional excretion of lithium increased during both unclamped (17.7 +/- 1.8 to 30.4 +/- 0.8%) and clamped (12.9 +/- 2.1 to 23.9 +/- 2.7%) periods. These studies demonstrate that atrial natriuretic peptide-induced natriuresis is importantly mediated by an increase in glomerular filtration rate and decrease in tubular reabsorption.

Maintenance of renal autoregulation during infusion of aminophylline or adenosine.

Adenosine has been postulated to link control of glomerular filtration rate (GFR) and renal blood flow (RBF) with changes in renal metabolism. In the present study, we examined the role of adenosine in renal autoregulation by comparing the responses of normal anesthetized dogs to step decreases in renal artery pressure (RAP) to the response obtained after receptor blockade of adenosine with aminophylline or by flooding the kidney with exogenous adenosine. In six dogs at normal RAP, intrarenal infusion of aminophylline (10 mumol/min) did not alter renal hemodynamics. GFR and RBF were well autoregulated (greater than 90% of control) at RAP values equal to or greater than 85 mmHg before and after aminophylline. At RAP equal to 75 mmHg, GFR and RBF decreased by 27 +/- 10 and 20 +/- 8%, respectively, before aminophylline and by 25 +/- 7 and 13 +/- 6% after aminophylline. In a different group of six dogs, intrarenal infusion of adenosine (6 mumol/min) significantly increased RBF (32 +/- 9%) and decreased GFR (38 +/- 10%) at normal RAP. However, GFR and RBF were both well autoregulated (greater than 90% of control) at RAP values equal to or greater than 85 mmHg before and after adenosine. At RAP equal to 75 mmHg, GFR and RBF decreased by 10 +/- 5 and 7 +/- 3%, respectively, before adenosine and by 12 +/- 6 and 17 +/- 5% after adenosine. Neither aminophylline nor adenosine attenuated the elevations in plasma renin activity associated with reductions in RAP. These data fail to provide evidence that adenosine is an important factor in autoregulation of GFR and RBF during acute reductions in RAP within the autoregulatory range.

Control of glomerular filtration rate: role of intrarenally formed angiotensin II

This study was designed to investigate the role of intrarenally formed angiotensin II (ANG II) in controlling glomerular filtration rate (GFR) during reduction of renal artery pressure (RAP). The experimental design prevented renin released by the kidney from entering the systemic circulation and therefore prevented changes in circulating ANG II from influencing GFR control. In dogs with only a functional intrarenal renin-angiotensin system (RAS), GFR and renal blood flow (RBF) were not significantly altered by RAP reduction to 70 mmHg. After blockade of intrarenal ANG II formation with SQ 14225, reduction of RAP to 70 mmHg decreased GFR and filtration fraction to 75.6 +/- 7.0 and 59.0 +/- 4.1% of control, respectively, while RBF remained at 129.3 +/- 8.8% of control. Calculated efferent arteriolar resistance decreased considerably more when RAP was reduced after SQ 14225, whereas preglomerular resistance decreased to about the same level as observed prior to SQ 14225 infusion. After return of endogenously produced ANG II by recirculation of the renal venous blood or after infusion of ANG II (following SQ 14225) at a rate that restored RBF to the control level (with RAP held at 70 mmHg in each case), GFR, filtration fraction, and calculated efferent resistance were restored to control levels, but preglomerular resistance did not change. These results suggest that intrarenal ANG II formation plays an important role in maintaining GFR during reductions in RAP by constricting efferent arterioles.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of intraarterial infusion of prostacyclin on the tubuloglomerular feedback control in the rat.

Effects of intraarterial prostacyclin (PGI2) infusions on interstitial hydrostatic and oncotic pressures and on the tubuloglomerular feedback (TGF) control of glomerular filtration rate (GFR) were studied in rat kidneys. The hilar lymph flow rate was used as a measure of interstitial hydrostatic pressure and the lymph protein concentration was used for interstitial oncotic pressure estimation. In the micropuncture experiments the stop-flow pressure technique was employed for determining the TGF characteristics, i.e. stop-flow pressure (PSF), maximal reduction of PSF (delta PSF) and turning point (TP), defined as the end-proximal flow rate at which 50% of delta PSF was obtained. Non-hypotensive doses of PGI2 (50 to 100 ng X kg-1 B.W. X min-1) infused in 30 min evoked an increase in urine and lymph flow rates and a decrease in lymph protein concentration, but did not affect GFR. delta PSF was reduced (9.9 +/- 1.0 mmHg versus 4.7 +/- 2.2 mmHg) and TP increased (22 +/- 2 nl/min versus 34 +/- 2 nl/min), but the PSF was unaffected. These changes were seen during the infusion period and during the immediate post-infusion control period of 30 min. Our data indicate that non-hypotensive doses of PGI2 in some way can affect the renal interstitial pressure and the TGF control system.

Endocrine control of glomerular filtration rate.

Endocrine control of glomerular filtration rate.